Green synthesis of Chlorin e6 and tests of its photosensitive bactericidal activities

Phototoxic treatments of pathogenic bacteria and fungi of trees induce oxidative damage that is preferable to toxic chemical treatment.Here,we used green methods to synthesize Chlorin e6 from chlorophyll a,which was extracted from crude silkworm excrement using concentrated(strong)alkali hydrolysis and acidification.The photosensitive bactericidal activities of the new chlorin were tested in vitro,and possible mechanisms of action are discussed.The results showed that Chlorin e6 can be lightactivated to have bactericidal activity against Escherichia coli,Bacillus subtilis and Fusarium oxysporum,but it had little bactericidal effect in the dark.This kind of chlorin compounds has great potential as a natural phototoxic antimicrobial compound to control harmful bacteria on the leaves in forestry systems.

Identification of a novel PAK1 inhibitor to treat pancreatic cancer

Pancreatic cancer is one of the most aggressive cancers with poor prognosis and a low 5-year survival rate.The family of P21-activated kinases(PAKs)appears to modulate many signaling pathways that contribute to pancreatic carcinogenesis.In this work,we demonstrated that PAK1 is a critical regulator in pancreatic cancer cell growth.PAK1-targeted inhibition is therefore a new potential therapeutic strategy for pancreatic cancer.Our small molecule screening identified a relatively specific PAK1-targeted inhibitor,CP734.Pharmacological and biochemical studies indicated that CP734 targets residue V342 of PAK1 to inhibit its ATPase activity.Further in vitro and in vivo studies elucidated that CP734 suppresses pancreatic tumor growth through depleting PAK1 kinase activity and its downstream signaling pathways.Little toxicity of CP734 was observed in murine models.Combined with gemcitabine or 5-fluorouracil,CP734 also showed synergistic effects on the anti-proliferation of pancreatic cancer cells.All these favorable results indicated that CP734 is a new potential therapeutic candidate for pancreatic cancer.

IL-6R blockade by chikusetsusaponin IVa butyl ester inhibits Th17 cell differentiation and ameliorates collagen-induced arthritis

Interleukin(IL)-6 is central to the pathogenesis of rheumatoid arthritis(RA).1 IL-6 receptor(IL-6R)blockade is an effective treatment strategy for RA based on the clinical efficacy of tocilizumab.However,serious infections are the most frequent adverse events associated with long-term monotherapy with tocilizumab,an exogenous biomacromolecule.2 Novel small-molecule IL-6R inhibitors with fewer deleterious side effects could therefore have potential as RA treatments.We previously identified chikusetsusaponin IVa butyl ester(CS)as a natural small-molecule IL-6R antagonist.3 Here,we assessed the effects of CS on a mouse model of collagen-induced arthritis(CIA)to evaluate its therapeutic potential against RA.The results showed that CS ameliorated arthritis in CIA mice by inhibiting T-helper 17(Th17)cell differentiation and could serve as a novel agent for treating RA.